The functional lumen imaging probe contractile response pattern is the best predictor of botulinum toxin response in esophagogastric junction outflow obstruction.

BACKGROUND: Esophagogastric junction outflow obstruction (EGJOO) is a heterogenous disorder in which the correct management strategy is unclear. We assessed whether functional lumen imaging probe (FLIP) topography data could select EGJOO, which would benefit from lower esophageal sphincter Botulinum toxin (Botox) injection. METHODS: This was a single-center prospective study of adult patients meeting Chicago Classification (CC) v3.0 criteria for EGJOO. We assessed differences in pretreatment physiologic measurements on high-resolution manometry (HRM) and FLIP and other relevant clinical variables in predicting Botox response (>50% in BEDQ at 2 months). KEY RESULTS: Sixty-nine patients were included (ages 33-90, 73.9% female). Of these, 42 (61%) were Botox responders. Majority of physiologic measures on HRM and FLIP and esophageal emptying were not different based on Botox response. However, a spastic-reactive (SR) FLIP contractile response (CR) pattern predicted a Botox response with OR 25.6 (CI 2.9-229.6) when compared to antegrade FLIP CR; and OR for impaired-disordered/absent CR was 22.5 (CI 2.5-206.7). Logistic regression model using backward elimination (p value = 0.0001, AUC 0.79) showed that a SRCR or IDCR/absent response and the upright IRP predicted Botox response. Response rates in tiered diagnostic groups were: (i) CCv3.0 EGJOO (60.9%), (ii) CCv4.0 EGJOO (73.1%), (iii) CCv4.0 + FLIP REO (80%), (iv) CCv4.0, FLIP REO, and abnormal FLIP CR (84.2%), and (v) CCv4.0, FLIP REO, and SR FLIP CR (90%). CONCLUSIONS AND INFERENCES: FLIP helps identify patients with EGJOO who are likely to response to LES Botox therapy. An abnormal FLIP contractile response pattern is the single-most important predictor of a Botox response.

Radial artery catheterization using a novel T-type ultrasound probe: a single-center randomized study.

Ultrasound guidance has been reported to facilitate radial artery catheterization compared with the palpation method. However, a recent meta-analysis showed that there was not significant differences in the first attempt success rate between the long-axis in-plane (LA-IP) method and the short-axis out-of-plane method. In 2023, we started using a novel T-type probe. We can recognize the needle first during the radial artery access with the short-axis view and then dose it with the long-axis view using the T-type probe. Therefore, we hypothesized that the T-type probe-guided method might heighten the first attempt success rate in radial artery catheterization, even for non-expert practitioners, compared with the LA-IP technique. One hundred and fifty adult patients, older than 20 years, ASA I to III, were randomly assigned to the T-type probe-guided group (Group T: n = 75) or the LA-IP group (Group L: n = 75). The primary outcome was the first attempt success rate. The first attempt success rate in Group T (49/71, 69%) was significantly higher than that in Group L (31/68, 46%) (p = 0.0062). The present study showed that the T-type probe might facilitate the radial artery catheterization rather than the LA-IP method.

Construction of UCNPs-aptamer-AuNPs luminescence energy transfer probe for ratio detection of Staphylococcus aureus.

A ratio luminescence probe was developed for detecting Staphylococcus aureus (S. aureus) based on luminescence energy transfer (LET) using double-wavelength emission (550 nm and 812 nm) upconversion nanoparticles (UCNPs) as donor, gold nanoparticles (AuNPs) as acceptor and the aptamer for S. aureus as the specific recognition and link unit. The LET process could cause luminescence quenching because of the spectral overlap between the acceptor and the donor at 550 nm. In the presence of S. aureus, S. aureus selectively combined with the aptamer, and the AuNPs left the surface of UCNPs, which weakened the quenching effect and restored the luminescence of UCNPs. Based on this, the ratio detection was realized by monitoring the change of the luminescence signal of the probe at 550 nm and taking the luminescence signal at 812 nm as the reference signal. Crucially, the probe has a fast reaction speed, with a reaction time of 25 min, and the detection of S. aureus is realized in the concentration range of 5.0 × 103-3.0 × 105 CFU/ml, with the detection limit of 106 CFU/ml. Therefore, the ratio probe has great potential for detecting of S. aureus in food because of its high sensitivity, fast speed and good selectivity.

Discovery and characterization of BRBV-sheep virus in nasal swabs from domestic sheep in China.

Introduction: The escalating occurrence of infectious disease outbreaks in humans and animals necessitates innovative, effective, and integrated research to better comprehend their transmission and dynamics. Viral infection in livestock has led to profound economic losses globally. Pneumonia is the prevalent cause of death in sheep. However, very few studies exist regarding virus-related pathogens in sheep. Metagenomics sequencing technologies in livestock research hold significant potential to elucidate these contingencies and enhance our understanding. Methods: Therefore, this study aims to characterize respiratory viromes in paired nasal swabs from Inner Mongolian feedlot sheep in China using metaviromic sequencing. Through deep sequencing, de novo assembly, and similarity searches using translated protein sequences, several previously uncharacterized and known viruses were identified in this study. Results: Among these discoveries, a novel Bovine Rhinitis B Virus (BRBV) (BRBV-sheep) strain was serendipitously detected in the nasal swabs of domestic sheep (Ovis aries). To facilitate further molecular epidemiological studies, the entire genome of BRBV-sheep was also determined. Owing to the unique sequence characteristics and phylogenetic position of BRBV-sheep, genetically distinct lineages of BRBV in sheep may exist. A TaqMan-based qRT-PCR assay targeting the 3D polymerase gene was developed and used to screen 592 clinical sheep specimens. The results showed that 44.59% of the samples (264/592) were positive. These findings suggest that BRBV sheep are widespread among Inner Mongolian herds. Conclusion: This discovery marks the initial identification of BRBV in sheep within Inner Mongolia, China. These findings contribute to our understanding of the epidemiology and genetic evolution of BRBV. Recognizing the presence of BRBV in sheep informs strategies for disease management and surveillance and the potential development of targeted interventions to control its spread.

Application of apical myocardial perfusion quantitative analysis by contrast-enhanced ultrasound utilizing high-frequency linear probe.

BACKGROUND: Due to insufficient near-field resolution and artifacts, it is challenging to evaluate the left ventricular apical perfusion with phased-array probes. By combining high-frequency linear probe and contrast-enhanced ultrasound (CEUS), imaging of apical myocardial perfusion could be improved. The study aims to evaluate the preliminary application of CEUS by high-frequency linear probes to assess the apical perfusion. METHODS: The study enrolled retrospectively 91 patients to test the feasibility of the novel method. In protocol 1, patients were stratified into a group with left anterior descending artery (LAD) stenosis (N = 40) and a group without LAD stenosis or coronary artery disease (N = 41) based on the degree of coronary artery narrowing, quantified by >50% stenosis in coronary angiography. Receiver operating characteristics (ROC) analysis was performed to test the diagnostic value of perfusion parameters. In protocol 2, the reproducibility of high-frequency linear probe in apical perfusion analysis was compared with the conventional phased-array probe in 30 patients. RESULTS: (1) The novel method is feasible in 81(89.01%) patients. (2) In protocol 1, to detect LAD stenosis, the best cut-off of ß, T, A, and MBF were 10.32, 3.28, 9.39, and 4.99, respectively. Area under the curve of ß, T, A, and MBF were .880, .881, .761, and .880, respectively. (3) In protocol 2, compared with phased-array probe, the quantitative analysis of high-frequency linear probe is of high reproducibility and could get good curve fitting (R2 = .29 vs. R2 = .71, P < .01). CONCLUSION: Observation of apical perfusion using this method is feasible and quantitative analysis allows an accurate and convenient identification of LAD stenosis. This method provides an alternative for patients who have difficulties in visualizing the apical region with a phased-array probe.

Modulating Carrier Dynamics in PdSe2: The Role of Pressure in Electronic and Phononic Interactions.

PdSe2 is a puckered transition metal dichalcogenide that has been reported to undergo a two-dimensional to three-dimensional structural transition under pressure. Here, we investigated the electronic and phononic evolution of PdSe2 under high pressure using pump-probe spectroscopy. We observed the electronic intraband and interband transitions occurring in the d orbitals of Pd, revealing the disappearance of the Jahn-Teller effect under high pressure. Furthermore, we found that the decay rates of interband recombination and intraband relaxation lifetimes change at 3 and 7 GPa, respectively. First-principles calculations suggest that the bandgap closure slows the decay rate of interband recombination after 3 GPa, while the saturation of phonon-phonon scattering is the main reason for the relatively constant intraband relaxation lifetime. Our work provides a novel perspective for understanding the evolution of the electron and modulation of the carrier dynamics by phonons under pressure.

A Ratiometric Benzimidazole-Based Fluorescent Probe for The Recognition of Phosgene in Solution and Gaseous Phases.

Considering the high toxicity and widespread application of phosgene, there is an urgent need to develop a simple and sensitive method for detecting phosgene. In this work, we designed and synthesized a novel ratiometric fluorescent probe 1 containing fluorophores of benzimidazole and benzothiazole. Probe 1 showed excellent sensitivity (< 30 s) and selectivity (LOD = 3.82 nM) for phosgene and significant ratiometric fluorescence changes. In addition, 1-loaded polystyrene membrane test strips were used to conveniently and efficiently detect phosgene gas (0.5 ppm) via the naked eye and the RGB APP of the smartphone, indicating that this probe has great potential for phosgene detection in the gaseous phase.

Solid-State NMR 13C sensitivity at high magnetic field.

Sensitivity is the foundation of every NMR experiment, and the signal-to-noise ratio (SNR) should increase with static (B0) magnetic field, by a proportionality that primarily depends on the design of the NMR probe and receiver. In the low B0 field limit, where the coil geometry is much smaller than the wavelength of the NMR frequency, SNR can increase in proportion to B0 to the power 7/4. For modern magic-angle spinning (MAS) probes, this approximation holds for rotor sizes up to 3.2 mm at 14.1 Tesla (T), corresponding to 600 MHz 1H and 151 MHz 13C Larmor frequencies. To obtain the anticipated benefit of larger coils and/or higher B0 fields requires a quantitative understanding of the contributions to SNR, utilizing standard samples and protocols that reproduce SNR measurements with high accuracy and precision. Here, we present such a systematic and comprehensive study of 13C SNR under MAS over the range of 14.1 to 21.1 T. We evaluate a range of probe designs utilizing 1.6, 2.5 and 3.2 mm rotors, including 24 different sets of measurements on 17 probe configurations using five spectrometers. We utilize N-acetyl valine as the primary standard and compare and contrast with other commonly used standard samples (adamantane, glycine, hexamethylbenzene, and 3-methylglutaric acid). These robust approaches and standard operating procedures provide an improved understanding of the contributions from probe efficiency, receiver noise figure, and B0 dependence in a range of custom-designed and commercially available probes. We find that the optimal raw SNR is obtained with balanced 3.2 mm design at 17.6 T, that the best mass-limited SNR is achieved with a balanced 1.6 mm design at 21.1 T, and that the raw SNR at 21.1 T reaches diminishing returns with rotors larger than 2.5 mm.

A Phase 2 Multicenter Clinical Trial of Intraoperative Molecular Imaging of Lung Cancer with a pH-Activatable Nanoprobe.

PURPOSE: Intraoperative molecular imaging (IMI) uses tumor-targeted optical contrast agents to improve identification and clearance of cancer. Recently, a probe has been developed that only fluoresces when activated in an acidic pH, which is common to many malignancies. We report the first multicenter Phase 2 trial of a pH-activatable nanoprobe (pegsitacianine, ONM-100) for IMI of lung cancer. METHODS: Patients with suspected or biopsy-confirmed lung cancer scheduled for sublobar resection were administered a single intravenous infusion of pegsitacianine (1 mg/kg) one to three days prior to surgery. Intraoperatively, the patients underwent a white light thoracoscopic evaluation, and then were imaged with an NIR thoracoscope to detect tumor fluorescence. The primary study endpoint was the proportion of patients with a clinically significant event (CSE) which was defined as an intraoperative discovery during IMI that led to a change in the surgical procedure. Possible CSEs included (i) localizing the index lung nodule that could not be located by white light, (ii) identifying a synchronous malignant lesion, or (iii) recognizing a close surgical margin (< = 10 mm). Secondary endpoints were sensitivity, specificity, NPV, and PPV of pegsitacianine in detecting tumor-containing tissue. The safety evaluation was based on adverse event reporting, clinical laboratory parameters, and physical examinations. RESULTS: Twenty patients were confirmed as eligible and administered pegsitacianine. Most of the patients were female (n = 12 [60%]), middle-aged (mean age 63.4 years), and former smokers (n = 13 [65%], 28.6 mean pack years). Mean lesion size was 1.9 cm, and most lesions (n = 17 [85%]) were malignant. The most common histologic subtype was adenocarcinoma (n = 9). By utilizing IMI with pegsitacianine, one patient had a CSE in the detection of a close margin and another had localization of a tumor not detectable by traditional surgical means. Six of 19 (31.6%) malignant lesions fluoresced with mean tumor-to-background ratio (TBR) of 3.00, as compared to TBR of 1.20 for benign lesions (n = 3). Sensitivity and specificity of pegsitacianine-based IMI for detecting malignant tissue was 31.6% and 33.3%, respectively. Positive predictive value (PPV) and negative predictive value (NPV) of pegsitacianine-based IMI was 75% and 7.1%, respectively. Pegsitacianine-based imaging was not effective in differentiating benign and malignant lymph nodes. From a safety perspective, no drug-related serious adverse events occurred. Four patients experienced mild pegsitacianine-related infusion reactions which required discontinuing the study drug with complete resolution of symptoms. CONCLUSIONS: Pegsitacianine-based IMI, though well tolerated from a safety perspective, does not consistently label lung tumors during resection and does not provide significant clinical benefit over existing standards of surgical care. The biology of lung tumors may not be as acidic as other solid tumors in the body thereby not activating the probe as predicted.

Evaluation of the FPMC respiratory panel for detection of respiratory tract pathogens in nasopharyngeal swab and sputum specimens.

OBJECTIVES: The performance of the new Respiratory Pathogen panel (fluorescent probe melting curve, FPMC) for the qualitative detection of 12 organisms (chlamydia pneumoniae, mycoplasma pneumoniae, adenovirus, influenza A virus, influenza B virus, parainfluenza virus, rhinovirus, etc.) was assessed. METHODS: Prospectively collected nasopharyngeal swab (NPS) and sputum specimens (n = 635) were detected by using the FPMC panel, with the Sanger sequencing method as the comparative method. RESULTS: The overall percent concordance between the FPMC analysis method and the Sanger sequencing method was 100% and 99.66% for NPS and sputum specimens, respectively. The FPMC testified an overall positive percent concordance of 100% for both NPS and sputum specimens. The FPMC analysis method also testified an overall negative percent concordance of 100% and 99.38% for NPS and sputum specimens, respectively. CONCLUSIONS: The FPMC analysis method is a stable and accurate assay for rapid, comprehensive detecting for respiratory pathogens.

A smart hypochlorous acid fluorescent probe enabling Ibuprofen-release for osteoarthritis theranostics.

Background: Osteoarthritis (OA) standing as the most prevalent form of arthritis, closely associates with heightened levels of reactive oxygen species, particularly hypochlorous acid (HOCl). Although there are numerous probes available for detecting HOCl in the OA region, probes with dual functions of diagnostic and therapeutic capabilities are still significantly lacking. While this type of probe can reduce the time gap between diagnosis and treatment, which is clinically needed. Methods: We developed a fluorescent probe (DHU-CBA1) toward HOCl with theranostics functions through the release of methylene blue (MB) and ibuprofen (IBP) in this work. DHU-CBA1 can detect HOCl with high specificity and sensitivity, releasing MB and IBP with an impressive efficiency of ≥ 95% in vitro. Results: DHU-CBA1 exhibits good biosafety, enabling in vivo imaging of endogenous HOCl, along with reducing arthritis scores, improving synovitis and cartilage damage, and maintaining catabolic balance while alleviating senescence in cartilage. Conclusions: This study proposes a novel approach to enhance osteoarthritis therapy by releasing IBP via a smart HOCl-enabled fluorescent probe.

Biomarker-driven molecular imaging probes in radiotherapy.

Background: Biomarker-driven molecular imaging has emerged as an integral part of cancer precision radiotherapy. The use of molecular imaging probes, including nanoprobes, have been explored in radiotherapy imaging to precisely and noninvasively monitor spatiotemporal distribution of biomarkers, potentially revealing tumor-killing mechanisms and therapy-induced adverse effects during radiation treatment. Methods: We summarized literature reports from preclinical studies and clinical trials, which cover two main parts: 1) Clinically-investigated and emerging imaging biomarkers associated with radiotherapy, and 2) instrumental roles, functions, and activatable mechanisms of molecular imaging probes in the radiotherapy workflow. In addition, reflection and future perspectives are proposed. Results: Numerous imaging biomarkers have been continuously explored in decades, while few of them have been successfully validated for their correlation with radiotherapeutic outcomes and/or radiation-induced toxicities. Meanwhile, activatable molecular imaging probes towards the emerging biomarkers have exhibited to be promising in animal or small-scale human studies for precision radiotherapy. Conclusion: Biomarker-driven molecular imaging probes are essential for precision radiotherapy. Despite very inspiring preliminary results, validation of imaging biomarkers and rational design strategies of probes await robust and extensive investigations. Especially, the correlation between imaging biomarkers and radiotherapeutic outcomes/toxicities should be established through multi-center collaboration involving a large cohort of patients.

Modularized supramolecular assemblies for hypoxia-activatable fluorescent visualization and image-guided theranostics.

Rationale: Molecular imaging of microenvironment by hypoxia-activatable fluorescence probes has emerged as an attractive approach to tumor diagnosis and image-guided treatment. Difficulties remain in its translational applications due to hypoxia heterogeneity in tumor microenvironments, making it challenging to image hypoxia as a reliable proxy of tumor distribution. Methods: We report a modularized theranostics platform to fluorescently visualize hypoxia via light-modulated signal compensation to overcome tumor heterogeneity, thereby serving as a diagnostic tool for image-guided surgical resection and photodynamic therapy. Specifically, the platform integrating dual modules of fluorescence indicator and photodynamic moderator using supramolecular host-guest self-assembly, which operates cooperatively as a cascaded "AND" logic gate. First, tumor enrichment and specific fluorescence turn-on in hypoxic regions were accessible via tumor receptors and cascaded microenvironment signals as simultaneous inputs of the "AND" gate. Second, image guidance by a lighted fluorescence module and light-mediated endogenous oxygen consumption of a photodynamic module as dual inputs of "AND" gate collaboratively enabled light-modulated signal compensation in situ, indicating homogeneity of enhanced hypoxia-related fluorescence signals throughout a tumor. Results: In in vitro and in vivo analyses, the biocompatible platform demonstrated several strengths including a capacity for dual tumor targeting to progressively facilitate specific fluorescence turn-on, selective signal compensation, imaging-time window extension conducive to precise normalized image-guided treatment, and the functionality of tumor glutathione depletion to improve photodynamic efficacy. Conclusion: The hypoxia-activatable, image-guided theranostic platform demonstrated excellent potential for overcoming hypoxia heterogeneity in tumors.

[Design and Development of a Heat Sealing System for Rapid Reuse of Ultrasonic Probes]. / è¶ å£°æŽ¢å¤´å¿«é€Ÿå¤ç”¨çƒ­å°ç³»ç»Ÿçš„è®¾è®¡ä¸Žç ”å‘.

Objective: Ultrasound diagnosis and treatment is easy to perform and takes little time. It is widely used in clinical practice thanks to its non-invasive, real-time, and dynamic characteristics. In the process of ultrasound diagnosis and treatment, the probe may come into contact with the skin, the mucous membranes, and even the sterile parts of the body. However, it is difficult to achieve effective real-time disinfection of the probes after use and the probes are often reused, leading to the possibility of the probes carrying multiple pathogenic bacteria. At present, the processing methods for probes at home and abroad mainly include probe cleaning, probe disinfection, and physical isolation (using probe covers or sheaths). Yet, each approach has its limitations and cannot completely prevent probe contamination and infections caused by ultrasound diagnosis and treatment. For example, when condoms are used as the probe sheath, the rate of condom breakage is relatively high. The cutting and fixing of cling film or freezer bags involves complicated procedures and is difficult to perform. Disposable plastic gloves are prone to falling off and causing contamination and are hence not in compliance with the principles of sterility. Furthermore, the imaging effect of disposable plastic gloves is poor. Therefore, there is an urgent need to explore new materials to make probe covers that can not only wrap tightly around the ultrasound probe, but also help achieve effective protection and rapid reuse. Based on the concept of physical barriers, we developed in this study a heat sealing system for the rapid reuse of ultrasound probes. The system uses a heat sealing device to shrink the protective film so that it wraps tightly against the surface of the ultrasound probe, allowing for the rapid reuse of the probe while reducing the risk of nosocomial infections. The purpose of this study is to design a heat sealing system for the rapid reuse of ultrasound probes and to verify its application effect on the rapid reuse of ultrasound probes. Methods: 1) The heat sealing system for the rapid reuse of ultrasound probes was designed and tested by integrating medical and engineering methods. The system included a protective film (a multilayer co-extruded polyolefin thermal shrinkable film) and a heat sealing device, which included heating wire components, a blower, a photoelectric switch, temperature sensors, a control and drive circuit board, etc. According to the principle of thermal shrinkage, the ultrasound probe equipped with thermal shrinkable film was rapidly heated and the film would wrap closely around the ultrasound probe placed on the top of the heat sealing machine. The ultrasound probe was ready for use after the thermal shrinkage process finished. Temperature sensors were installed on the surface of the probe to test the thermal insulation performance of the system. The operation procedures of the system are as follows: placing the ultrasound probe covered with the protective film in a certain space above the protective air vent, which is detected by the photoelectric switch; the heating device heats the thermal shrinkable film with a constant flow of hot air at a set temperature value. Then, the probe is rotated so that the thermal shrinkable film will quickly wrap around the ultrasound probe. After the heat shrinking is completed, the probe can be used directly. 2) Using the convenience sampling method, 90 patients from the Department of Anesthesiology and Perioperative Medicine, the First Affiliated Hospital of Xi'an Jiaotong University were included as the research subjects. All patients were going to undergo arterial puncture under ultrasound guidance. The subjects were divided into 3 groups, with 30 patients in each group. Three measures commonly applied in clinical practice were used to process the probes in the three groups and water-soluble fluorescent labeling was applied around the puncture site before use. In the experimental group, the probes were processed with the heat sealing system. The standard operating procedures of the heat sealing system for rapid reuse of ultrasonic probes were performed to cover the ultrasonic probe and form a physical barrier to prevent probe contamination. There were two control groups. In control group 1, disinfection wipes containing double-chain quaternary ammonium salt were used to repeatedly wipe the surface of the probe for 10-15 times, and then the probe was ready for use once it dried up. In the control group 2, a disposable protective sheath was used to cover the front end of the probe and the handle end of the sheath was tied up with threads. Comparison of the water-soluble fluorescent labeling on the surface of the probe (which reflected the colony residues on the surface of the probe) before and after use and the reuse time (i.e., the lapse of time from the end of the first use to the beginning of the second use) were made between the experimental group and the two control groups. Results: 1) The temperature inside the ultrasound probe was below 40 ℃ and the heat sealing system for rapid reuse did not affect the performance of the ultrasound probe. 2) The reuse time in the heat sealing system group, as represented by (median [P25, P75]), was (8.00 [7.00, 10.00]) s, which was significantly lower than those of the disinfection wipe group at (95.50 [8.00, 214.00]) s and the protective sleeve group at (25.00 [8.00, 51.00]) s, with the differences being statistically significant (P<0.05). No fluorescence residue was found on the probe in either the heat sealing system group or the protective sheath group after use. The fluorescence residue in the heat sealing system group was significantly lower than that in the disinfection wipes group, showing statistically significant differences (χ 2=45.882, P<0.05). Conclusion: The thermal shrinkable film designed and developed in this study can be cut and trimmed according to the size of the equipment. When the film is heated, it shrinks and wraps tightly around the equipment, forming a sturdy protective layer. With the heat sealing system for rapid reuse of ultrasonic probes, we have realized the semi-automatic connection between the thermal shrinkable film and the heating device, reducing the amount of time-consuming and complicated manual operation. Furthermore, the average reuse time is shortened and the system is easy to use, which contributes to improvements in the reuse and operation efficiency of ultrasound probes. The heat sealing system reduces colony residues on the surface of the probe and forms an effective physical barrier on the probe. No probes were damaged in the study. The heat sealing system for rapid reuse of ultrasonic probes can be used as a new method to process the ultrasonic probes.

Visualization of cysteine in AD mouse with a high-quantum yield NIR fluorescent probe.

Alzheimer's disease (AD) has gradually received enthusiastic attention with the aging process, and studying its biological relevance is expected. Excitingly, fluorescence probes were considered to be powerful tools for exploring biological correlations. Therefore, a highly selective near-infrared (NIR) fluorescent probe (DCM-Cl-Acr) for imaging cysteine (Cys) in AD was designed and synthesized. Through structural optimization, the probe exhibited high fluorescence quantum yield and low detection limit (20 nM) towards Cys. Meanwhile, based on the high selectivity and high sensitivity response exhibited by the probe to Cys, it was successfully applied to visualize endogenous and exogenous Cys in living cells and zebrafish, and showed good discrimination from homocysteine (Hcy) and glutathione (GSH). Further, the correlation between AD and Cys concentration was clarified by imaging studies in hippocampus tissue of AD mouse, and the abnormal accumulation of Cys in the hippocampus of AD brain was demonstrated.

A novel AIE-based mitochondria-targeting fluorescent probe for monitoring of the fluctuation of endogenous hypochlorous acid in ferroptosis models.

Ferroptosis is a way of cell death mainly due to the imbalance between the production and degradation of lipid reactive oxygen species, which is closely associated with various diseases. Endogenous hypochlorous acid (HOCl) mainly produced in mitochondria is regarded as an important signal molecule of ferroptosis. Therefore, monitoring the fluctuation of endogenous HOCl is beneficial to better understand and treat ferroptosis-related diseases. Inspired by the promising aggregation-induced emission (AIE) properties of tetraphenylethene (TPE), herein, we rationally constructed a novel AIE-based fluorescent probe, namely QTrPEP, for HOCl with nice mitochondria-targeting ability and high sensitivity and selectivity. Probe QTrPEP consisted of phenylborate ester and the AIE fluorophore of quinoline-conjugated triphenylethylene (QTrPE). HOCl can brighten the strong fluorescence through a specific HOCl-triggered cleavage of the phenylborate ester bond and release of QTrPE, which has been demonstrated by MS, HPLC, and DLS experiments. In addition, combining QTrPE-doped test strips with a smartphone-based measurement demonstrated the excellent performance of the probe to sense HOCl. The obtained favorable optical properties and negligible cytotoxicity allowed the use of this probe for tracking of HOCl in three different cells. In particular, this work represents the first AIE-based mitochondria-targeting fluorescent probe for monitoring the fluctuation of HOCl in ferroptosis.

Ultrafast Visual Detection of a Trace Amount of Water by Highly Efficient Hybrid Manganese Halides.

A quantitative water detection method is urgently needed in storage facilities, space exploration, and the chemical industry. Although numerous physical techniques have been widely utilized to determine the water content, they still suffer from many disadvantages such as highly expensive special instruments, complicated analysis processes, etc. Hence, a convenient, rapid, and sensitive water analysis method is highly desirable. Herein, we developed a visual fluorescence sensing technology for water detection based on reversible PL off-on switching of organic-inorganic hybrid zero-dimensional (0D) manganese halides. In this work, a family of hybrid manganese halides were synthesized through a facile solution method, namely, [NH4(18-Crown-6)]2MnBr4, [Ca(18-Crown-6)·3H2O](18-Crown-6)MnBr4, [NH4(dibenzo-18-Crown-6)]2MnBr4, and [Ca(dibenzo-18-Crown-6)·2H2O]MnBr4. Excited by UV light, these highly crystalline manganese halides exhibit strong green light emissions from the d-d electron transition of Mn2+ with near-unity photoluminescence quantum yield and submillisecond lifetime. Benefiting from the dynamic and weak ionic bonding interactions, these 0D manganese halides display reversible water-response on/off luminescence switching but fail in any other aprotic solvents. Therefore, these 0D hybrid manganese halides can be explored as ultrafast visual fluorescence probes to detect the trace amount of water in organic solvents with multiple superiorities of rapid response time (< 2 s), ultralow detection limit (9.71 ppm), excellent repeatability, etc. The reversible water-response luminescent on/off switching also provides a binary optical gate with advanced applications in anticounterfeiting and information security, etc.

High positive predictive value of CNVs detected by clinical exome sequencing in suspected genetic diseases.

BACKGROUND: Genetic disorders often manifest as abnormal fetal or childhood development. Copy number variations (CNVs) represent a significant genetic mechanism underlying such disorders. Despite their importance, the effectiveness of clinical exome sequencing (CES) in detecting CNVs, particularly small ones, remains incompletely understood. We aimed to evaluate the detection of both large and small CNVs using CES in a substantial clinical cohort, including parent-offspring trios and proband only analysis. METHODS: We conducted a retrospective analysis of CES data from 2428 families, collected from 2018 to 2021. Detected CNV were categorized as large or small, and various validation techniques including chromosome microarray (CMA), Multiplex ligation-dependent probe amplification assay (MLPA), and/or PCR-based methods, were employed for cross-validation. RESULTS: Our CNV discovery pipeline identified 171 CNV events in 154 cases, resulting in an overall detection rate of 6.3%. Validation was performed on 113 CNVs from 103 cases to assess CES reliability. The overall concordance rate between CES and other validation methods was 88.49% (100/113). Specifically, CES demonstrated complete consistency in detecting large CNV. However, for small CNVs, consistency rates were 81.08% (30/37) for deletions and 73.91% (17/23) for duplications. CONCLUSION: CES demonstrated high sensitivity and reliability in CNV detection. It emerges as an economical and dependable option for the clinical CNV detection in cases of developmental abnormalities, especially fetal structural abnormalities.

Effects of Co on Mechanical Properties and Precipitates in a Novel Secondary-Hardening Steel with Duplex Strengthening of M2C and ß-NiAl.

Synergistic strengthening of nano-scaled M2C and ß-NiAl has become a new route to develop ultra-high secondary-hardening steel. At present, the effect of Co on the synergistic precipitation behavior of duplex phases of M2C and ß-NiAl has been rarely reported. This paper revealed the effects of Co on the mechanical properties and duplex precipitates of M2C and ß-NiAl in a novel 2.5 GPa ultra-high strength secondary-hardening steel. The tensile tests indicated that a 10% Co-alloy steel achieved a much stronger secondary-hardening effects compared to a Co-free steel during aging process, especially in the early-aging state. Needle-shaped M2C and spherical ß-NiAl particles were observed in both Co-alloy and Co-free steels. However, the number density, and volume fraction of M2C were significantly enhanced in the 10% Co-alloy steel. The Mo contents in M2C carbide and α-Fe after aging treatment were both analyzed through experimental determination and thermodynamic calculation, and the results indicated that Co decreased the solubility of Mo in α-Fe, thus promoting the precipitation of Mo-rich carbides.

A Ratiometric Fluorescent Probe Dye-Functionalized MOFs Integrated with Logic Gate Operation for Efficient Detection of Acetaldehyde.

Volatile organic compounds (VOCs) are a class of hazardous gases that are widely present in the atmosphere and cause great harm to human health. In this paper, a ratiometric fluorescent probe (Dye@Eu-MOFs) based on a dye-functionalized metal-organic framework was designed to detect VOCs, which showed high sensitivity and specificity for acetaldehyde solution and vapor. A linear correlation between the integrated fluorescence intensity (I510/I616) and the concentration of acetaldehyde was investigated, enabling a quantitative analysis of acetaldehyde in the ranges of 1 × 10-4~10-5 µL/mL, with a low detection limit of 8.12 × 10-4 mg/L. The selective recognition of acetaldehyde could be clearly distinguished by the naked eye under the excitation of UV light. The potential sensing mechanism was also discussed. Significantly, a molecular logic gate was constructed based on the whole system, and finally, a molecular logic network system for acetaldehyde detection connecting basic and integrated logic operations was realized. This strategy provided an effective guiding method for constructing a molecular-level logic gate for acetaldehyde detection on a simple platform.